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Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis

Bone Marrow Transplantation volume 57, pages 911–917 (2022)Cite this article

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Abstract

Acute Myeloid Leukemia (AML) has a median age at diagnosis of 67 years. The most common curative therapy remains an allogeneic hematopoietic stem cell transplantation (HCT), yet it is complicated by treatment-related mortality (TRM) and ongoing morbidity including graft versus host disease (GVHD) that may impact survival, particularly in older patients. We examined the outcomes and predictors of success in 1321 patients aged 60 years and older receiving a HCT for AML in first complete remission (CR1) from 2007-2017 and reported to the CIBMTR. Outcomes were compared in three age cohorts (60–64; 65–69; 70+). With median follow-up of nearly 3 years, patients aged 60–64 had modestly, though significantly better OS, DFS and lower TRM than those either 65–69 or 70+; cohorts with similar outcomes. Three-year OS for the 3 cohorts was 49.4%, 42.3%, and 44.7% respectively (p = 0.026). TRM was higher with increasing age, cord blood as graft source and HCT-CI score of ≥3. Conditioning intensity was not a significant predictor of OS in the 60-69 cohort with 3-year OS of 46% for RIC and 49% for MAC (p = 0.38); MAC was rarely used over age 70. There was no difference in the relapse rate, incidence of Grade III/IV acute GVHD, or moderate-severe chronic GVHD across the age cohorts. After adjusting for other predictors, age had a small effect on OS and TRM. High-risk features including poor cytogenetics and measurable residual disease (MRD) prior to HCT were each significantly associated with relapse and accounted for most of the adverse impact on OS and DFS. Age did not influence the incidence of either acute or chronic GVHD; while graft type and associated GVHD prophylaxis were most important. These data suggest that age alone is not a barrier to successful HCT for AML in CR1 and should not exclude patients from HCT. Efforts should focus on minimizing residual disease and better donor selection.

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Fig. 1: Survival outcomes of 1321 AML undergoing HCT in CR1.
Fig. 2: Relapse and treatment related mortality.
Fig. 3: Graft versus host disease.

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Funding

The CIBMTR is supported primarily by Public Health Service U24CA076518 from the National Cancer Institute (NCI), the National Heart, Lung and Blood Institute (NHLBI) and the National Institute of Allergy and Infectious Diseases (NIAID); HHSH250201700006C from the Health Resources and Services Administration (HRSA); and N00014-20-1-2705 and N00014-20-1-2832 from the Office of Naval Research; Support is also provided by Be the Match Foundation, the Medical College of Wisconsin, the National Marrow Donor Program, and from the following commercial entities: AbbVie; Actinium Pharmaceuticals, Inc.; Adaptive Biotechnologies Corporation; Adienne SA; Allovir, Inc.; Amgen, Inc.; Angiocrine Bioscience; Astellas Pharma US; Bluebird Bio, Inc.; Bristol Myers Squibb Co.; CSL Behring; CytoSen Therapeutics, Inc.; Daiichi Sankyo Co., Ltd.; Eurofins Viracor; ExcellThera; Fate Therapeutics; Gamida-Cell, Ltd.; Genentech Inc; GlaxoSmithKline; Incyte Corporation; Janssen/Johnson & Johnson; Jasper Therapeutics; Jazz Pharmaceuticals, Inc.; Karyopharm Therapeutics; Kiadis Pharma; Kite, a Gilead Company; Kyowa Kirin; Legend Biotech; Magenta Therapeutics; Medac GmbH; Merck & Co.; Millennium, the Takeda Oncology Co.; Miltenyi Biotec, Inc.; MorphoSys; Novartis Pharmaceuticals Corporation; Omeros Corporation; Oncoimmune, Inc.; Orca Biosystems, Inc.; Pfizer, Inc.; Pharmacyclics, LLC; Sanofi Genzyme; Seagen, Inc.; Stemcyte; Takeda Pharmaceuticals; Tscan; Vertex; Vor Biopharma; Xenikos BV.

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Authors and Affiliations

  1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA

    Joseph E. Maakaron

  2. CIBMTR® (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Mei-Jie Zhang, Karen Chen, Wael Saber & Daniel Weisdorf

  3. Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA

    Mei-Jie Zhang

  4. University of Kansas Cancer Center, Westwood, KS, USA

    Sunil Abhyankar

  5. The Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA

    Vijaya Raj Bhatt

  6. Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Saurabh Chhabra

  7. University of Minnesota Blood and Marrow Transplant Program—Adults, Minneapolis, MN, USA

    Najla El Jurdi, Fiona He & Mark Juckett

  8. Division of Hematology and Oncology, Indiana University School of Medicine, Indianapolis, IN, USA

    Sherif S. Farag

  9. Ohio State Medical Center, James Cancer Center, Cleveland, OH, USA

    Marcos de Lima

  10. Blood & Marrow Transplant Program, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, USA

    Navneet Majhail

  11. Department of Internal Medicine, Division of Hematology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands

    Marjolein van der Poel

  12. Division of Hematology, Ohio State University, Columbus, OH, USA

    Ayman Saad

  13. Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin Savani

  14. Division of Hematology/Oncology/Cell Therapy, Rush University, Chicago, IL, USA

    Celalettin Ustun

  15. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, GA, USA

    Edmund K. Waller

  16. Division of Hematology and Transplant Center, Mayo Clinic Rochester, Rochester, MN, USA

    Mark Litzow

  17. Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Partow Kebriaei

  18. Laboratory of Myeloid Malignancies, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA

    Christopher S. Hourigan

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Correspondence to Daniel Weisdorf.

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Competing interests

Daniel Weisdorf reports grants from FATE Therapeutics, grants from Incyte, outside the submitted work. Christopher S Hourigan reports other from Sellas, outside the submitted work. Joseph E Maakaron reports other from CRISPR, other from FortySeven Inc., other from TALARIS, outside the submitted work. Marcos de Lima reports grants from Pfizer grants from Celgene, personal fees from Kadmon personal fees from Pfizer, personal fees from Incyte, personal fees from BMS, outside the submitted work. Vijaya Raj Bhatt reports personal fees from Agios, grants and personal fees from Incyte, personal fees from Takeda, personal fees from Partner Therapeutics, personal fees from Omeros, grants and personal fees from Abbvie, grants from Jazz, grants from National Marrow Donor Program, other from Oncoceutics, personal fees from Partnership for health analytic research, LLC, grants and other from Pfizer, personal fees from CSL Behring, grants from Tolero Pharmaceuticals, personal fees from Rigel Pharmaceuticals, other from Novartis, personal fees from Genentech, outside the submitted work. Ayman Saad reports personal fees from Magenta Therapeutics, personal fees from Incyte Pharmaceuticals, personal fees from CareDx, outside the submitted work. Partow Kebriaei reports grants from Amgen, grants from Ziopharm, other from Kite, other from Novartis, other from Jazz, other from Pfizer, outside the submitted work. Celalettin Ustun reports not relevant, but honoria from Novartis and Blueprint for attending advisory board meeting. Fiona He reports personal fees from Magenta Therapeutics, outside the submitted work. Sunil Abhyankar reports other from Incyte Corporation, other from Therkos, outside the submitted work. Navneet Majhail reports personal fees from lncyte, personal fees from Anthem, Inc., personal fees from Nkarta, personal fees from Mallinckrodt, outside the submitted work.

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Maakaron, J.E., Zhang, MJ., Chen, K. et al. Age is no barrier for adults undergoing HCT for AML in CR1: contemporary CIBMTR analysis. Bone Marrow Transplant 57, 911–917 (2022). https://doi.org/10.1038/s41409-022-01650-5

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